Blinatumomab salvage therapy appears effective in progressive non-Hodgkin lymphoma subtype

Blinatumomab demonstrated safety and efficacy as a second salvage therapy in patients with relapsed or refractory B-cell non-Hodgkin lymphoma and progressive disease, according to findings presented at the ASH Annual Meeting and Exposition.

Responders had predominantly progressive disease after initial salvage therapy with two or more cycles of platinum-based chemotherapy.

“Patients without complete metabolic response to first salvage therapy have limited options and poor outcomes based on historical data,” the researchers wrote. “Blinatumomab ... has demonstrated a survival benefit in B-cell acute lymphoblastic leukemia and has antitumor activity in patients with relapsed, refractory aggressive B-cell non-Hodgkin lymphoma, including patients previously treated with autologous HSCT. This open-label, multicenter, phase 2 portion of an adaptive phase 2/3 study assessed the efficacy and safety of blinatumomab as a second salvage therapy.”

Luke Coyle, MBBS, FRACP, FRCPA, of the department of hematology at Royal North Shore Hospital in Sydney, and colleagues enrolled 41 patients aged 18 years or older with biopsy-confirmed relapsed, refractory aggressive B-cell non-Hodgkin lymphoma who did not experience complete remission or complete metabolic response following first-line therapy with an anthracycline and an anti-CD20 agent. Patients had either progressive metabolic disease, partial metabolic response (according to the Lugano classification) or no metabolic response following two or more cycles of platinum-based initial salvage therapy. Patients treated previously with radiotherapy were PET-positive 6 or more weeks after the last dose of therapy.

Most patients (66%) had progressive metabolic disease or progressive disease. Five patients (12%) experienced no metabolic response; nine patients (22%) had partial metabolic response.

Blinatumomab (Blincyto, Amgen) was administered via continuous intravenous infusion for the single 70-day first cycle. Doses during the first cycle included 9 g/day for 7 days, 28 g/day for 7 days and 112 g/day for 42 days, followed by a 14-day treatment-free interval. A 28-day second cycle was optional and included the following doses: 9 g/day for 7 days, 28 g/day for 7 days and 112 g/day for 14 days.

Complete metabolic response as assessed by central PET served as the primary endpoint. Other endpoints included objective response rate (calculated as complete metabolic response plus partial metabolic response), post-response hematopoietic stem cell transplant realization rates and the rate/severity of adverse events.

All patients were treated with blinatumomab; 19 (46%) finished the first cycle of treatment. Discontinuation of therapy during the first cycle occurred in 22 patients. The majority (n = 17) stopped therapy because of disease progression; four patients halted therapy because of adverse events and there was one death. In patients who discontinued therapy in the first cycle because of disease progression, eight patients (47%) finished at least 90% of the planned treatment period. In addition, four patients began the second cycle of treatment and three of them completed it. One patient stopped treatment during the second cycle because of adverse events.

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ORR within 12 weeks of initiating treatment with blinatumomab was 37% (95% CI, 22% to 53%). Nine patients (22%) reached complete metabolic response.

Eight patients (20%) achieved HSCT remission, including seven patients (17%) with autologous HSCT (complete metabolic response, n = 6; partial metabolic response, n = 1) and one patient with allogeneic HSCT in partial metabolic response. However, most patients (n = 35) either did not undergo HSCT (n = 32) or underwent delayed HSCT (n = 3) because of progressive metabolic disease (n = 17), lack of complete metabolic response (n = 4), adverse events (n = 4), patient preference (n = 1), no metabolic response or unknown (n = 1) or other (n = 8). Information was missing for one patient.

Among the nine patients who achieved a complete metabolic response, eight (89%) were alive and did not relapse over a median follow-up period of 8.8 months. The Kaplan-Meier estimate at 9 months was 51%; median OS was not reached.

Grade 3 or greater treatment-related adverse events occurred in 24 patients (59%). Neurologic events, which aligned with earlier reports of blinatumomab, were seen in 23 patients (56%), including 10 (24%) with grade 3 neurological events and 3 (7%) with neurological events that led to treatment termination. One patient developed grade 3 cytokine release syndrome. Other grade 3 or greater adverse events included infections (n = 8; 20%), bone marrow toxicity (n = 7; 17%), thromboembolic events (n = 3; 7%), hepatic disorders (n = 2; 5%) and acute pancreatitis (n = 1; 2%).

Grade 4 or greater treatment-related adverse events were seen in 10 patients (24%). Treatment discontinuation because of adverse events occurred in 7 patients (17%).

“Blinatumomab monotherapy as [second salvage] therapy induced complete metabolic response/partial metabolic response in 37% of patients and led to HSCT in 20%,” the researchers wrote. “When considering that 66% of the patients enrolled had progressive disease and that 47% received the therapeutic dose, blinatumomab showed promising efficacy ... and potentially offers a treatment option for patients unresponsive to standard salvage regimens.” - by Julia Ernst, MS

Reference:

Coyle L, et al. Abstract 400. Presented at: ASH Annual Meeting and Exposition; Dec. 1-4, 2018; San Diego.

Disclosures: Coyle reports a non-financial relationship with Amgen. Please see the abstract for all other authors’ relevant financial disclosures.